TGFβ Polymorphism and Radiation-Induced Fibrosis in Breast Cancer

In an analysis reported in JAMA Oncology, Benjamin D. Smith, MD, of the Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, and colleagues found that a single nucleotide polymorphism (C−509T) in the transforming growth factor β1 (TGFβ1) gene was associated with higher risk of radiation-induced fibrosis in women with early breast cancer.

The current study was a prespecified analysis of a randomized trial comparing hypofractionated whole-breast irradiation (WBI; 42.56 Gy in 16 fractions) with conventionally fractionated WBI (50 Gy in 25 fractions) after breast-conserving surgery in 287 women aged ≥ 40 years with stage 0 to IIA breast cancer enrolled from February 2011 to February 2014. The primary outcome was grade ≥ 2 breast fibrosis at 3 years after radiotherapy.

Fibrosis Risk

Among the 287 women, TGFβ1 genotype was available for 174; of these, 89 patients (51%) had at least 1 copy of C−509T, including 48% of the conventionally fractionated WBI group and 54% of the hypofractionated WBI group with available data. Among patients patients with TGFβ1 genotype data and 3-year radiotherapy toxicity data, grade 2 or higher breast fibrosis was present in 12 (13.8%) of 87 evaluable patients with C−509T vs 3 (3.8%) of 80 evaluable patients without the allele variant (absolute difference = 10.0%, P = .02). On multivariate analysis, only presence of C−509T (odds ratio [OR] = 4.47, P = .02) and fair to poor baseline panel physician-assessed postoperative cosmesis (OR = 7.09, P < .001) were significantly associated with risk of breast fibrosis.

The investigators concluded, “To date, this study seems to be the first prospective validation of a genomic marker for radiation fibrosis. The C−509T allele in TGFβ1 is a key determinant of breast fibrosis risk. Assessing TGFβ1 genotype may facilitate a more personalized approach to locoregional treatment decisions in breast cancer.” ■